Research Articles (Medical Microbiology)

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Reply to Datta, “Is static or cidal antibiotic falsifiable?”
Spellberg, Brad; Wald-Dickler, Noah; Holtom, Paul; Meyer-Sautter, Pascal; Camp, Austin; Diaz Diaz, Alejandro; Buhamad, Ranya; Meza Vazquez, Ali Sebastian; Aguirre-Garcia, Gloria Mayela; Stanton, Matthew; Butler-Wu, Susan M.; Chiu, Isabelle; Ergenc, Zeynep; Bhoojhawon, Guru; Murri, Rita; Maraolo, Alberto Enrico; Cabanilla, Gabriela; Riccardi, Niccolò; Tshisevhe, Vhudzani; Behenna, Curtis; Williams, Karen S.; Kufel, Wesley D.; Wojciaczyk, Natalia; Pimentel, Bernardo Vidal; Muyidi,, Ahmed; Costa, Rodrigo P.L.; Motta, Fabrizio; Bortolussi-Courval, Émilie; Lee, Todd C.; McDonald, Emily G.; Ghanem, Bassam; Nelson, Zachary (American Society for Microbiology, 2025-11)
We would like to thank Dr. Datta for his interest in our article. Dr. Datta wishes to defend the static vs. cidal antibiotic model against “absolutist framing.” He invokes “mono-parametric” assays like “MBC/MIC ratios or…reactive oxygen species generation” to suggest that in vitro static vs. cidal phenomenology may be phenotypically real.
Whole-genome sequencing for surveillance of Salmonella at a public health institution in South Africa
Smith, Anthony Marius; Sekwadi, Phuti; Ngomane, Hlengiwe M.; Disenyeng, Bolele; Erasmus, Linda K.; Thomas, Juno; Bogoshi, Dineo; Smouse, Shannon L.; Tau, Nomsa P. (AOSIS, 2025-12-09)
BACKGROUND : Whole-genome sequencing (WGS) is transforming communicable disease surveillance globally. The National Institute for Communicable Diseases, South Africa, participates in national laboratory-based surveillance for human isolates of Salmonella. OBJECTIVE : This study was to investigate human Salmonella isolates from South Africa, 2020–2023, using WGS analysis. METHODS : WGS was performed using Illumina NextSeq Technology. Data were analysed using multiple bioinformatics tools, including those available at the Center for Genomic Epidemiology, Pathogenwatch and EnteroBase. Data analysis allowed for identification and characterisation of isolates. Core-genome multilocus sequence typing was used to investigate the phylogeny of isolates. RESULTS : Of the 8006 isolates of Salmonella that were analysed using WGS, 130 distinctive serovars and subspecies were identified. Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) (4271/8006; 53.3%) and Salmonella Typhimurium (1430/8006; 17.9%) were the most prevalent serovars, accounting for 71.2% of all isolates. This was followed by Salmonella Typhi (482/8006; 6.0%). Sixteen per cent (1288/8006) of isolates showed the presence of antimicrobial resistance (AMR) determinants associated with ≥ 2 classes of antimicrobials. Salmonella Isangi (167/8006; 2.1%) showed the highest prevalence of AMR, with most isolates (159/167; 95.2%) showing AMR determinants associated with ≥ 7 classes of antimicrobials. Core-genome multilocus sequence typing was used to confirm several suspected clusters and outbreaks and identified additional cryptic or unreported clusters and outbreaks. Investigation of clusters and outbreaks mostly involved Salmonella Enteritidis and Salmonella Typhi. CONCLUSION : The implementation of WGS has enabled genomic surveillance of Salmonella, which allows for enhanced characterisation and AMR determination of isolates and identification of clusters and outbreaks, which informs targeted public health investigation and response. What this study adds: This study describes the population structure of Salmonella isolated from humans in South Africa and hugely contributes to the available Salmonella WGS data from Africa.
A retrospective analysis of uropathogens isolated and antimicrobial susceptibility patterns at a regional hospital in North West province, South Africa
Teixeira, Miguel J.; Pretorius, Vian; Hunt, Robert C.J.G.; Morar, Sanam; Colloty, Jamie; Radebe, Caleb M.; Morar, Rajen (AOSIS, 2025-11-30)
BACKGROUND : Urinary tract infections are among the most common infections affecting the general population. Their high incidence, as well as frequent antimicrobial use, contribute significantly to the development of antimicrobial resistance (AMR). OBJECTIVE : To determine the profile and prevalence of uropathogens isolated from urine specimens at a regional hospital and assess susceptibility patterns to commonly used antimicrobials recommended by the National Essential Medicines List (NEML). METHODS : This was a retrospective evaluation of laboratory reports for all urine specimens submitted between 01 January 2020 and 31 December 2023. RESULTS : The most frequently cultured organisms were Escherichia coli (n = 1481; 42%); Klebsiella pneumoniae (n = 568; 16%); Enterococcus faecalis (n = 249; 7%); Proteus mirabilis (n = 229; 7%), Enterobacter cloacae (n = 137; 4%), and Candida albicans (n = 119; 3%). Escherichia coli maintained high sensitivity to antimicrobials such as nitrofurantoin (92.2%) and gentamicin (90.6%), whilst K. pneumoniae had decreased sensitivities of 40% and 77%, respectively. Cumulative sensitivities of commonly used first-line antimicrobials showed low rates of susceptibility to ciprofloxacin (77%), nitrofurantoin (67%), and amoxicillin/clavulanate (68.7%). CONCLUSION : Escherichia coli was the most commonly identified isolate and remains sensitive to nitrofurantoin. It was, however, resistant to ciprofloxacin, amoxicillin/clavulanate, and trimethoprim sulfamethoxazole, as were all the other Gram-negative organisms. These sensitivity patterns do not align with the antimicrobials recommended in the current NEML guidelines, and highlight the need for targeted therapy and interventions. What this study adds: This retrospective analysis identifies predominant uropathogens’ updated antimicrobial susceptibility profiles, some of which misalign with NEML guidelines. Insights will guide targeted antimicrobial stewardship, empiric therapy, and local surveillance to curb AMR.
Lactobacillus-rich cervicovaginal microbiome associated with lower BV, HPV, and cytology outcomes in women
Osei Sekyere, John; Trama, Jason; Adelson, Martin; Trikannad, Charulata; DiBlasi, Desiree; Schuster, Rachel; Yang, Jing Jing; Mordechai, Eli (Elsevier, 2025-10-17)
The cervicovaginal microbiome modulates susceptibility to bacterial vaginosis (BV), high-risk human papillomavirus (hrHPV) infection, and epithelial cell abnormalities that precede cervical cancer. We retrospectively analyzed 15 607 qPCR-profiled cervicovaginal specimens from U.S. women (ages 14–95; 32 states) and integrated microbiome abundances, hrHPV genotyping, Pap-cytology, and demographics. BV was present in 53% and hrHPV in 11% of samples. Lactobacillus crispatus, L. gasseri, and L. jensenii were enriched in BV-negative and cytologically normal (NILM) samples, whereas L. iners and BV-associated anaerobes co-occurred with hrHPV and abnormal cytology. Machine-learning models confirmed age, hrHPV status, and L. crispatus abundance as the strongest multivariate predictors of BV and cytological outcomes (BV AUROC ≈0.97). Interaction analyses revealed synergistic associations between specific hrHPV genotypes and Gardnerella/Fannyhessea that further increased cytological risk. These findings underscore the clinical value of microbiome profiling and support probiotic strategies that promote protective Lactobacillus communities to reduce BV and hrHPV-related cervical pathology.
Prevalence of colistin resistance in multidrug-resistant Klebsiella pneumoniae recovered from clinical samples in Africa
Gashaw, Yalewayker; Asmare, Zelalem; Sisay, Asefa; Getatachew, Ermias; Gedfie, Solomon; Ashagre, Agenagnew; Bitew, Getachew; Tigabie, Mitkie; Reta, Melese Abate (Oxford University Press, 2025-08)
BACKGROUND : Colistin resistance in multidrug-resistant (MDR) Klebsiella pneumoniae is a growing concern in Africa, complicating treatment and public health management. Colistin is a last-resort antibiotic for Gram-negative infections, but its resistance in clinical settings presents significant challenges. This study aims to determine the pooled prevalence of colistin resistance in MDR K. pneumoniae isolates from clinical specimens in Africa. METHODS : Articles were sourced from PubMed, Scopus, ScienceDirect and Google Scholar. Studies included were those reporting colistin resistance in MDR K. pneumoniae from clinical specimens in Africa, using EUCAST and CLSI-standard drug susceptibility testing. Data were extracted into Excel and analysed using STATA 17 with a random-effects model to determine the pooled prevalence. Heterogeneity was assessed using the I2 statistic, and publication bias was checked with Egger’s test. Subgroup analyses were performed to explore heterogeneity. RESULTS : The study analysed data from 30 articles on colistin resistance in MDR K. pneumoniae. The pooled prevalence was 21.59% (95% CI: 12.12–31.06), with high heterogeneity (I2 = 99.71%). Sub-regional variation was significant (P < 0.001), with prevalence rates differing across regions: 42.34% in East Africa, 37.1% in West Africa, 17.1% in Southern Africa and 13.0% in North Africa. Country-specific rates were highest in Nigeria (39.12%), followed by Kenya (22.52%), South Africa (17.12%) and Egypt (14.0%) (P < 0.001). CONCLUSIONS : Colistin resistance in MDR K. pneumoniae is high in Africa, with notable regional differences. The study calls for strict colistin regulations, robust antimicrobial stewardship and rapid diagnostic tools for resistance detection.
Nocardia species epidemiology and susceptibility profiles from 2019 to 2022 in South Africa
Thomas, T.; Lowe, M.; Le Roux, K.; Strydom, Kathy-Anne (South african Medical Association, 2025-08)
BACKGROUND : Nocardia species cause infections in humans, from localised to disseminated disease. They constitute a public health threat owing to the lack of sufficient information about them. In South Africa (SA), the last publication on this organism was in 2010. Predominant species types and antibiotic susceptibilities may have changed over this period. OBJECTIVE : To address the knowledge gap surrounding Nocardia species and their antibiotic susceptibilities in SA. METHODS : This was a retrospective and cross-sectional study. Data were collected from the Central Data Warehouse (CDW) of the National Health Laboratory Service (NHLS) on suspected Nocardia species from 1 January 2019 to 31 December 2022. Organism speciation was performed using 16S rRNA sequencing and antibiotic susceptibility testing (AST) by the broth microdilution (BMD) method. Data analysis included patient age, sample types from which the organism was cultured, distribution in the various SA provinces, species types and species AST profiles, including a record of trimethoprim-sulfamethoxazole (TMP/SMX) non-susceptibility. RESULTS : One hundred and sixty-five positive culture results were analysed. The majority of positive cultures (28%, n=46) were from the 30 - 39-year age group. The organism was predominantly cultured from pus samples (31%, n=51). The top two provinces from which the largest numbers of isolates were submitted were Gauteng (69%, n=114) and Western Cape (18%, n=30) provinces. Two percent (n=4) of isolates were not sequenced, and 18% (n=30) of isolates lacked AST results. Twenty-nine percent (n=47) of the Nocardia species that were sequenced could not be speciated using 16S rRNA sequencing. The top two species country-wide were N. abscessus complex (25%, n=42) and N. cyriacigeorgica (18%, n=29). Approximately 90% (n=121) of all isolates tested were TMP/SMX susceptible. CONCLUSION : The predominant isolation of Nocardia species from pus samples suggests that the majority were deep-seated infections. The most common Nocardia species types and the AST profiles have changed over time. The study highlights the need for alternative methods for the speciation of this organism.
Spectrum of sexual partner types among adults screened for sexually transmitted infections in the Eastern Cape, South Africa
De Vos, Lindsey; Mdingi, Mandisa M.; Gigi, Ranjana M.S.; Gebengu, Avuyonke; Peters, Remco P.H. (Public Library of Science, 2025-05-07)
In South Africa, Chlamydia trachomatis prevalence is 14.7% in women and 6.6% in men, while Neisseria gonorrhoeae rates are 6.0% and 3.4%. Partner management, including identifying and screening for STIs, is essential for STI control efforts but challenging due to relationship dynamics, fear of disclosure and stigma. This study aims to understand how adults in the Eastern Cape report partner types when seeking STI care, enhancing partner notification strategies and reducing transmission. From February-August 2023, a cross-sectional evaluation of a Neisseria gonorrhoeae lateral flow assay was conducted among asymptomatic adults aged 18-49 years at four primary healthcare facilities in Buffalo City, Eastern Cape. Participants completed surveys classifying partners into LUSTRUM team's 8 partner types and 5 type-classifications. Data were analyzed using StataSE 17, examining associations between partner types and variables like gender, location, number of sexual partners, and STI test results. A total of 500 men and 400 women (median ages 31 and 32) were recruited. The most reported partner types were main/serious/long-term partners (41%) and girlfriend/boyfriend (29%) or LUSTRUM's 4: established (67%) and occasional partners (28%). Participants reporting main/long-term partners, steady, or boyfriend/girlfriend showed variability in partner numbers. Male adults more commonly reported casual partner types like friends with benefits (21% vs. 9%) and fuck buddy/booty call (9% vs. 3%), with significant associations for super casual/hook-up/meet/one-night stand (p = 0.02). Regional differences in partner types and a significant association between new partners and NG Xpert positivity (p = 0.01) were observed. This study confirms the diverse spectrum of sexual partner types. Findings reveal that men and women may have different relationships, and regional variations suggest context-specific approaches are needed. Identifying partner types can enhance communication and treatment strategies and address significant gaps in partner notification and STI care.
Mobile genetic elements of global Escherichia coli ST131 clades with carbapenemases
Peirano, Gisele; Matsumara, Yasufumi; Pitout, Johann D.D. (Springer, 2025-09)
Please read abstract in the article.
Genomic epidemiology of Pseudomonas aeruginosa sequence type 111
Matsumara, Yasufumi; Peirano, Gisele; Kock, Marleen M.; Pitout, Johann D.D. (Springer, 2025-02)
Please read abstract in the article.
Molecular epidemiology of global carbapenemase-producing Serratia spp. (2015-2017)
Peirano, Gisele; Matsumura, Yasufumi; Pitout, Johann D.D. (Springer, 2025-12)
Please read abstract in the article.
Value of a commercial multiplex molecular panel for the diagnosis of cholera in an outbreak setting in Hammanskraal, Tshwane, South Africa
Safiyyah, Khan; Skosana, Lebogang Busisiwe; Colloty, Jamie; Nchabeleng, Maphoshane; Ntlemo, Grace; Said, Mohamed (Elsevier, 2025-09)
Cholera is not endemic in South Africa. However, between February and July 2023, 1073 suspected cholera cases, and 198 laboratory-confirmed cases were reported nationally. This is the first report of the use of a commercial, rapid diagnostic assay in an outbreak setting. This method evaluation study was conducted at the National Health Laboratories Service (NHLS) Tshwane Microbiology laboratory in Pretoria, South Africa, during the outbreak period. Eighteen retrospective stored culture-positive Vibrio cholerae isolates and 102 prospective clinical specimens were processed on the EntericBio® Dx panel (Serosep, Limerick, Ireland) as well as the gold standard of culture. For the EntericBio® processing, stools were processed according to the manufacturer’s instructions. Real time polymerase chain reaction (PCR) was performed on the Roche LightCycler®. The diagnostic performance was compared between culture and the EntericBio® Dx assay. All discrepant results were resolved at a referral laboratory using an in-house PCR assay. The mean time to results using EntericBio® was 48 h earlier than culture results. Overall, the EntericBio® Dx panel demonstrated a sensitivity of 100 % for the detection of Vibrio species when compared to culture. Although the EntericBio® platform reported the results as Vibrio species, the pre-test probability was high for V. cholerae in an outbreak setting. Further serotyping methods have confirmed this. The quick turnaround time and excellent sensitivity of the EntericBio® platform expedites patient treatment and institution of appropriate infection control practices and has potential to rapidly control such outbreaks.
Effect of contraceptive methods on the vaginal microbiome and host immune factors
Serrano, Myrna G.; Edwards, David; Ahmed, Khatija; Bailey, Veronique C.; Beksinska, Mags; Edupuganti, Laahirie; Harryparsad, Rushil; D'Hellencourt, Florence L.; Meyer, Bahiah; Mehou-Loko, Celia; Radzey, Nina; Taku, Ongeziwe; Williamson, Anna-Lise; Smit, Jennifer; Spaine, Katherine; Zhu, Bin; Jefferson, Kimberly K.; Nanda, Kavita; Strauss III, Jerome F.; Morrison, Charles S.; Deese, Jennifer; Masson, Lindi; Buck, Gregory A.; Deese, Jennifer; Masson, Lindi; Buck, Gregory A. (Elsevier, 2025-08)
OBJECTIVE : The objective of this study was to assess alterations in vaginal microbiota and immune markers over the first 3 months following initiation of copper intrauterine device (copper IUD), levonorgestrel (LNG) implant, and intramuscular depot medroxyprogestone acetate (DMPA-IM). STUDY DESIGN : We included 162 participants from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, which enrolled healthy, HIV-negative women seeking contraception and randomized them to a copper IUD, LNG implant, or DMPA-IM. Microbiome and immune profiles in vaginal swab samples collected at enrollment, 1 month and 3 months were analyzed. We categorized microbiome profiles as ‘‘optimal’’, ‘‘intermediate’’, or ‘‘non-optimal’’ based on established criteria [1]. We compared microbiome and immune markers across contraceptive groups and evaluated changes to 1 and 3 months. RESULTS : Copper IUD users had a more diverse vaginal microbiome and generally increased inflammatory cytokines and antimicrobial peptides over the 3-month follow-up, compared to LNG-implant and DMPA-IM users [2]. LNG-implant users had less complex vaginal microbiomes with reduced inflammation, while DMPA-IM showed little change in either microbiome composition or inflammatory markers. Copper IUD users exhibited lower microbiome stability and a higher likelihood of transitioning to less optimal profiles. In contrast, LNG-implant users showed greater stability and a higher probability of transition to optimal microbiome and immune marker profiles. CONCLUSIONS : Contraceptive methods affect the vaginal microbiome differently. Copper IUD use may lead to less favorable profiles and increased levels of some immune markers, indicating potential adverse health effects. Conversely, LNG-implant usage promotes a more favorable microbiome and immune marker balance. IMPLICATIONS : Our findings suggest that copper IUDs are associated with decreased prevalence of Lactobacillus-dominated microbiomes, higher transition rates towards less optimal microbiome and increased inflammatory profiles, which may lead to negative implications for gynecologic and reproductive health, the LNG-implant may offer positive health benefits with increased prevalence of L. crispatus-dominated microbiomes.
Using sputum and tongue swab specimens for in-home point-of- care targeted universal testing for tuberculosis of household contacts : an acceptability and feasibility analysis
Bezuidenhout , Charl; Long, Lawrence; Nichols, Brooke; Meyer-Rath, Gesine; Fox, Matthew P.; Olifant, Sharon; Theron, Grant; Fiphaza, Kuhle; Pieruccini, Maria; Ruhwald, Morten; Penn-Nicholson, Adam; Fourie, Bernard P.; Medina-Marino, Andrew (BMJ Publishing Group, 2025-08-21)
INTRODUCTION : Effective strategies are essential for early tuberculosis (TB) detection. Reliance on passive case detection, symptom screening and collection of sputum results in delayed or undiagnosed TB, contributing to on-going TB transmission. This study assessed the acceptability of in-home targeted universal TB testing (TUTT) using GeneXpert MTB/RIF Ultra at point-of-care (POC) during household contact investigations (HCIs) and the feasibility of using sputum and tongue swab specimens. METHODS : The TB Home Study sought to evaluate the predictive value of different specimen types for use as a household-level triage test for TB. Household contacts of people with TB residing in the Buffalo City Metro Health District (Eastern Cape Province, South Africa) who received in-home POC TUTT through the TB Home Study were asked to complete a post-test acceptability survey. The survey assessed the level of comfort, confidence in the test results and perceived appropriateness of in-home POC TUTT. A feasibility framework was used to assess the feasibility of using sputum and tongue swab specimens for testing. RESULTS : Of the 325 eligible household contacts, 281/325 (86.5%) provided consent. Of those contacts, 278/281 (98.9%) provided a tongue swab, and 50/281 (17.8%) could expectorate sputum. All specimens were successfully prepared for immediate in-home testing. Of the 172 tongue swab-based tests performed, 169 (98.3%) produced a valid result, whereas 47 of 49 (95.9%) sputum-based tests had a valid result. An immediate tongue swab-based test result was available for 274/278 (98.6%) clients compared with 47/49 (95.9%) sputum-based test results. The mean in-home POC TUTT acceptability score (5=highly acceptable) was 4.2/5 (SD=0.4). CONCLUSION : In-homePOC TUTT using sputum and tongue swab specimens was highly acceptable and feasible. Tongue swabs greatly increased the testing rates owing to the high sample collection yield. Combining sputum and tongue swabs for in-home POC testing offers a promising strategy to improve TB case detection and reduce diagnostic delays.
Electro-impedimetric detection of human anti-mycolate antibody biomarkers of TB before, during, and after treatment
Baumeister, Carl Robert; Verschoor, Jan Adrianus; Ueckermann, Veronica; Molatseli, Mosa; Sesing, Thoriso; Khuboni, Nomthandazo; Fourie, Bernard P. (Taylor and Francis, 2025)
Efficient TB management requires rapid and accurate diagnosis of active pulmonary and extrapulmonary TB at the point-of-care. Blood-based antibody biomarker assays may be ideal if unaffected by HIV co-infection and antibody memory from prior TB or vaccination. AIM : This study assessed electro-impedimetric detection (EIS-MARTI) of anti-mycolate antibodies (AMAb) in TB patients before, during, and after treatment, compared to sputum culture (MGIT) as the gold standard. METHODS : A prospective pilot study enrolled 15 confirmed TB patients and 73 healthy controls at a Pretoria hospital (2016–2017). A prospective monitoring study followed 25 confirmed TB patients over 6 months of treatment at a Pretoria clinic (2019–2020) to evaluate biomarker behavior. Outcomes were analyzed using descriptive statistics, wherein diagnostic accuracy and predictive values were assessed by ROC curve analysis. RESULTS : EIS-MARTI detected 14/15 true TB-positive cases independent of HIV co-infection and 68/73 true TB-negatives in the pilot study. In the monitoring study, EIS-MARTI correlated with culture in 7/8 cases at treatment end, but not during the first 2 months. CONCLUSION : AMAbs arise independently of HIV co-infection in active TB, recede during treatment, and are rapidly detected by a hand-held EIS-MARTI device. While suitability for treatment monitoring remains uncertain, EIS-MARTI shows promise for rapid, accurate TB diagnosis and confirming cure. PLAIN LANGUAGE SUMMARY : The purpose of this work was to investigate anti-mycolate antibodies as a suitable biomarker for diagnosing tuberculosis, monitoring treatment, and screening people at risk for TB.
Empowering women's PrEP choices : qualitative insights into long-acting PrEP preferences and decision-making during pregnancy and breastfeeding in South Africa and Botswana
Chen-Charles, Jenny; De Vos, Lindsey; Vundhla, Prisca; Gebengu, Avuyonke; Rousseau, Elzette; Bekker, Linda-Gail; Peters, Remco P.H.; Mussa, Aamirah; Morroni, Chelsea; Toska, Elona; Babalola, Chibuzor M.; Klausner, Jeffrey D.; Davey, Dvora Joseph (Springer, 2026-01)
Pregnant and breastfeeding women (PBW) are at heightened risk of HIV acquisition. We aimed to explore PBW’s preferences of various long-acting PrEP modalities. In-depth interviews were conducted with PBW at three sites: Cape Town, East London (South Africa), and Gaborone (Botswana). We conducted thematic analysis, guided by the Health Belief Model, to examine participants’ HIV risk perception during pregnancy and breastfeeding, their perceived individual-level facilitators and barriers of each PrEP modality, and the support needed by participants for PrEP uptake and continuation. 40 participants were interviewed, aged 18–39 years (mean 27 years), including 13 adolescent girls and young women (AGYW; 18–24 years). Participants were either pregnant (n = 20) or breastfeeding (n = 20). Perceived HIV risk during pregnancy motivated PrEP use. Long-acting methods were preferred over daily pills for convenience and perceived reliability, with injectables most favoured due to familiarity with contraceptive injections. However, concerns about pain and side effects persisted. Monthly oral PrEP was seen as easier than daily pills but raised similar concerns about adherence. Implants were met with fear and mistrust, often rooted in negative contraceptive experiences, though some valued their long-term protection. The vaginal ring was least acceptable due to unfamiliarity and discomfort with insertion. Participants emphasised the importance of external support (e.g. reminders), privacy and discretion, and community transparency to support PrEP adherence and reduce stigma. Addressing barriers – especially concerns about the safety and effectiveness of new modalities and challenges around adherence – could help improve strategies to better assist PBW in utilising long-acting PrEP modalities.
No evidence of MMR induced trained immunity to prevent SARS COV2 : results from a multi-centre RCT
Delany-Moretlwe, Sinead; Dehbi, Hakim-Moulay; Sikazwe, Izukanji; Kyei, George; Koram, Kwadwo; Dubberke, Erik; Mwelase, Noluthando; Hague, Dominic;; Bekker, Linda-Gail; Yun, Linda; Nel, Annalene; Du Toit, Leon; Biccard, Bruce; Gill, Katherine; Chipeta, Chikumbutso; Mngadi, Kathryn T.; Lebina, Limakatso; Dassaye, Reshmi; Asari, Villeshni; Fry, Samantha H.; Turton, Edwin; Ahmed, Khatija; Kusi, Kwadwo; Adu-Amankwah, Susan; Chilengi, Roma; Chilekwa, Joyce Chinyama; Lovat, Laurence; McGuckin, Dermot; Caverly, Emilia; Politi, Mary; Swan, Ben; DeSchryver, Anne; Mckinnon, Sherry; Gupta, Ananya; Jones, Gemma; Freemantle, Nicholas; Khader, Shabaana; Rees, Helen; Netea, Mihai G.; Moonesinghe, S. Ramani; Avidan, Michael S. (Frontiers Media, 2025-09-16)
BACKGROUND : Measles-containing vaccines (MCV), by training innate immune cells, are hypothesized to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). METHODS : In this international, double-blind, placebo-controlled trial, we randomly assigned adults, 18 years and older, to receive MCV or saline. The primary outcome was polymerase chain reaction (PCR) confirmed symptomatic COVID-19, up to 60 days after intervention. Secondary outcomes were PCR-confirmed symptomatic COVID-19 and serologically confirmed SARS-CoV-2 infection, up to 150 days after intervention. RESULTS : Of 3411 randomised participants, the modified intention-to-treat population included 1607 in the MCV and 1545 in the saline group. The estimated risk of symptomatic COVID-19 by 60 days was 1.5% in the MCV and 1.2% in the saline group (risk difference, 0.3 percentage points, 95% CI, -0.5 to 1.1; p=0.52). At 150 days, these percentages were 4.1% (65/1585) and 4.1% (64/1544) in the MCV and saline groups, respectively (risk difference, 0.04 percentage points, 95% CI, -1.4 to 1.3; p=0.95). Based on serology results available at 0 and 150 days, 10.6% (100/945) of participants in the MCV and 10.3% (98/951) in the saline group had infection with SARS-CoV-2 over the course of the trial (risk difference, 0.3 percentage points, 95% CI, -2.6 to 3.1; p=0.84). Three patients were hospitalised with COVID-19 disease in the MCV and one in the saline group. CONCLUSIONS : Administering MCVs to stimulate trained immunity did not prevent COVID-19 or SARS-CoV2 infection. Stimulating trained immunity might not be useful for preventing respiratory illness during future pandemics. CLINICAL TRIAL REGISTRATION : https://clinicaltrials.gov/, identifier NCT04333732.
Rapidly spreading Enterobacterales with OXA-48-like carbapenemases
Peirano, Gisele; Pitout, Johann D.D. (American Society for Microbiology, 2025-02)
Enterobacterales (mostly Klebsiella pneumoniae, Escherichia coli) with OXA-48-like carbapenemases (e.g., OXA-48, -181, -232, -244) are undermining the global efficiency of carbapenem therapy. In the Middle East, North Africa, and some European countries, OXA-48-like carbapenemases are the most common types of carbapenemases among Enterobacterales. Currently, OXA-48 is endemic in the Middle East, North Africa, Spain, France, and Belgium; OXA-181 is endemic in Sub-Saharan Africa and the Indian Subcontinent, while OXA-232 has been increasing in the Indian Subcontinent. European countries (e.g., Germany, Denmark, Switzerland, France) are experiencing community outbreaks with E. coli ST38 that produce OXA-244, and these strains have been introduced into Norwegian, Polish, and Czech hospitals. The global ascendancy of OXA-48-like genes is due to the combination of carbapenemases with horizontal spread through promiscuous plasmids (e.g., IncL, IncX3, ColE2) and vertical spread with certain high-risk multidrug-resistant clones (e.g., K. pneumoniae ST14, ST15, ST147, ST307; E. coli ST38, ST410). This is a powerful “gene survival strategy” that has assisted with the survival of OXA-48-like genes in different environments including the community setting. The laboratory diagnosis is complex; therefore, bacteria with “difficult to detect” variants (e.g., OXA-244, OXA-484) are likely underreported and are spreading silently “beneath the radar” in hospital and community settings. K. pneumoniae and E. coli with OXA-48-like carbapenemases are forces to be reckoned with.
The emerging concern of IMP variants being resistant to the only IMP-type metallo-β-lactamase inhibitor, xeruborbactam
Le Terrier, Christophe; Drusin, Salvador I.; Nordmann, Patrice; Pitout, Johann D.D.; Peirano, Gisele; Vila, Alejandro J.; Moreno, Diego M.; Poirel, Laurent (American Society for Microbiology, 2025-07)
Metallo-β-lactamases (MBLs) of IMP type are not inhibited by currently commercialized β-lactamase inhibitors, including taniborbactam (TAN), which inhibits only NDM- and VIM-type enzymes. However, the development of xeruborbactam (XER), which additionally inhibits IMP enzymes, may provide effective drug combinations such as meropenem-XER (MEM-XER) against most MBL producers. Thirty-two IMP-producing clinical gram-negative isolates were tested for MEM-XER. Susceptibility testing of β-lactams with TAN or XER at 4 or 8 µg/mL was performed. Noticeably, MEM-XER remained ineffective against all IMP-producing Pseudomonas aeruginosa isolates. By contrast, supplementation with XER significantly lowered MEM MICs for several IMP-producing Enterobacterales isolates, except for isolates and recombinant E. coli strains producing IMP-6, IMP-10, IMP-14, and IMP-26. Interestingly, IMP-59 producers showed susceptibility to both TAN- and XER-based combinations, although IMP enzymes are not supposed to be inhibited by TAN. Determinations of 50% inhibitory concentration (IC50) values of XER showed values being >15-fold higher for IMP-6, IMP-10, IMP-14, and IMP-26 compared with IMP-1. Interestingly, the IC50 value of TAN for IMP-59 was found in the same range as that for NDM-1 (7 µM). Finally, structural analyses and molecular modeling simulations indicated that the Ser262Gly mutation in IMP-6 may alter the electronic properties of the active site, whereas the Phe residue in IMP-10 may exert a steric effect counteracting XER binding. Resistance to XER in IMP-6, IMP-10, IMP-14, and IMP-26 variants, conferring resistance to MEM-XER, might be considered a serious concern since MEM-XER will be supposed to be a salvage therapy for MBL-, and especially IMP-producing Enterobacterales infections.
Static vs. cidal : it's not complex; it's simply incorrect
Spellberg, Brad; Wald-Dickler, Noah; Holtom, Paul; Meyer-Sautter, Pascal; Camp, Austin; Diaz, Alejandro Diaz; Buhamad, Ranya; Vazquez, Ali Sebastian Meza; Aguirre-Garcia, Gloria Mayela; Stanton, Matthew; Butler-Wu, Susan M.; Chiu, Isabelle; Ergenc, Zeynep; Bhoojhawon, Guru; Murri, Rita; Maraolo, Alberto Enrico; Cabanilla, Gabriela; Riccardi, Niccolo; Tshisevhe, Vhudzani; Behenna, Curtis; Williams, Karen S.; Kufel, Wesley D.; Wojciaczyk, Natalia; Pimentel, Bernardo Vidal; Muyidi, Ahmed; Costa, Rodrigo P.L.; Motta, Fabrizio; Bortolussi-Courval, Emilie; Lee, Todd C.; Mcdonald, Emily; Ghanem, Bassam; Nelson, Zachary (American Society for Microbiology, 2025-08)
No abstract available.
Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy : a systematic analysis for the Global Burden of Disease Study 2021
Ledesma, Jorge R.; Ma, Jianing; Zhang, Meixin; Basting, Ann V.L.; Chu, Huong Thi; Vongpradith, Avina; Novotney, Amanda; LeGrand, Kate E.; Xu, Yvonne Yiru; Dai, Xiaochen; Nicholson, Sneha Ingle; Stafford, Lauryn K.; Carter, Austin; Ross, Jennifer M; Abbastabar, Hedayat; Richard Gyan , Meriem; Abdulah, Deldar Morad; Aboagye, Richard Gyan; Abolhassani, Hassan; Abrha, Woldu Aberhe; Abubaker Ali, Hiwa; Abu-Gharbieh, Eman; Aburuz, Salahdein; Addo, Isaac Yeboah; Adepoju, Abiola Victor; Adhikari, Kishor; Adnani, Qorinah Estiningtyas Sakilah; Adra, Saryia; Afework, Abel; Aghamiri, Shahin; Agyemang-Duah, Williams; Ahinkorah, Bright Opoku; Ahmad, Danish; Ahmad, Sajjad; Ahmadzade, Amir Mahmoud; Ahmed, Haroon; Ahmed, Mohammed; Ahmed, Ayman; Akinosoglou, Karolina; AL-Ahdal, Tareq Mohammed Ali; Alam, Nazmul; Albashtawy, Mohammed; AlBataineh, Mohammad T.; Al-Gheethi, Adel Ali Saeed; Ali, Abid; Ali, Endale Alemayehu; Ali, Liaqat; Ali, Zahid; Ali, Syed Shujait Shujait; Allel, Kasim; Altaf, Awais; Al-Tawfiq, Jaffar A.; Alvis-Guzman, Nelson; Alvis-Zakzuk, Nelson J.; Amani, Reza; Amusa, Ganiyu Adeniyi; Amzat , Jimoh; Andrews, Jason R.; Anil, Abhishek; Anwer, Razique; Aravkin, Aleksandr Y; Areda, Damelash; Artamonov, Anton A.; Aruleba, Raphael Taiwo; Asemahagn, Mulusew A.; Atre, Sachin R.; Aujayeb, Avinash; Azadi, Davood; Azadnajafabad, Sina; Azzam, Ahmed Y.; Badar, Muhammad; Badiye, Ashish D.; Bagherieh, Sara; Bahadorikhalili, Saeed; Baig, Atif Amin; Banach, Maciej; Banik, Biswajit; Bardhan, Mainak; Barqawi, Hiba Jawdat; Basharat, Zarrin; Baskaran, Pritish; Basu, Saurav; Beiranvand, Maryam; Belete, Melaku Ashagrie; Belew, Makda Abate; Belgaumi, Uzma Iqbal; Beloukas, Apostolos; Bettencourt, Paulo J G; Bhagavathula,, Akshaya Srikanth; Bhardwaj, Nikha; Bhardwaj, Pankaj; Bhargava, Ashish; Bhat, Vivek; Bhatti, Jasvinder Singh; Bhatti, Gurjit Kaur; Bikbov, Boris; Bitra, Veera R.; Bjegovic-Mikanovic, Vesna; Buonsenso, Danilo; Burkart, Katrin; Bustanji, Yasser; Butt, Zahid A.; Camargos, Paulo; Cao, Yu; Carr, Sinclair; Carvalho, Felix; Cegolon, Luca; Cenderadewi, Muthia; Cevik, Muge; Chahine, Yaacoub; Chattu, Vijay Kumar; Ching, Patrick R.; Chopra, Hitesh; Chung, Eunice; Claassens, Mareli M.; Coberly, Kaleb; Cruz-Martins, Natália; Dabo, Bashir; Dadana, Sriharsha; Dadras, Omid; Darban, Isaac; Darega Gela, Jiregna; Darwesh, Aso Mohammad; Dashti, Mahmood; Demessa, Berecha Hundessa; Demisse, Biniyam; Demissie, Solomon; Derese, Awoke Masrie Asrat; Deribe, Kebede; Desai, Hardik Dineshbhai; Devanbu, Vinoth Gnana Chellaiyan; Dhali, Arkadeep; Dhama, Kuldeep; Dhingra, Sameer; Do, Thao Huynh Phuong; Dongarwar, Deepa; Dsouza, Haneil Larson; Dube, John; Dziedzic, Arkadiusz Marian; Ed-Dra, Abdelaziz; Efendi, Ferry; Effendi, Diyan Ermawan; Eftekharimehrabad, Aziz; Ekadinata, Nopryan; Ekundayo, Temitope Cyrus; Elhadi, Muhammed; Elilo, Legesse Tesfaye; Emeto, Theophilus I.; Engelbert Bain, Luchuo; Fagbamigbe, Adeniyi Francis; Fahim, Ayesha; Feizkhah, Alireza; Fetensa, Getahun; Fischer, Florian; Gaipov, Abduzhappar; Gandhi, , , Aravind P.; Gautam, Rupesh K.; Gebregergis, Miglas W.; Gebrehiwot, Mesfin; Gebrekidan, Kahsu Gebrekirstos; Ghaffari, Kazem; Ghassemi, Fariba; Ghazy, Ramy Mohamed; Goodridge, Amador; Goyal, Anmol; Guan, Shi-Yang; Gudeta, Mesay Dechasa; Guled, Rashid Abdi; Gultom, Novianti Br; Gupta, Veer Bala; Gupta, Vivek Kumar; Gupta, Sapna; Hagins, Hailey; Hailu, Semira Goitom; Hailu, Wase Benti; Hamidi, Samer; Hanif, Asif; Harapan, Harapan; Hasan, Rumina Syeda; Hassan, Shoaib; Haubold, Johannes; Hezam, Kamal; Hong, Sung Hwi; Horita, Nobuyuki; Hossain, Md Belal; Hosseinzadeh, Mehdi; Hostiuc, Mihaela; Hostiuc, Sorin; Huynh , Hong-Han; Ibitoye, Segun Emmanuel; Ikuta, Kevin S.; Ilic, Irena M.; Ilic, Milena D; Islam, Md Rabiul; Ismail, Nahlah Elkudssiah; Ismail, Faisal; Jafarzadeh, Abdollah; Jakovljevic, Mihajlo; Jalili, Mahsa; Janodia, Manthan Dilikumar; Jomehzadeh, Nabi; Jonas, Jost B.; Joseph, Nitin; Joshua, Charity Ehimwenma; Kabir, Zubair; Kamble, Bhushan Dattatray; Kanchan, Tanuj; Kandel, Himal; Kanmodi, Kehinde Kazeem; Kantar, Rami S.; Karaye, Ibraheem M.; Karimi Behnagh, Arman; Kassa, Gebrehiwot G.; Kaur, Rimple Jeet; Kaur, Navjot; Khajuria, Himanshu; Khamesipour , Faham; Khan, Yusra H.; Khan, M. Nuruzzaman; Khan Suheb, Mahammed Ziauddin; Khatab, Khaled; Khatami, Fatemeh; Kim, Min Seo; Kosen, Soewarta; Koul, Parvaiz A.; Koulmane Laxminarayana, Sindhura Lakshmi; Krishan, Kewal; Kucuk Bicer, Burcu; Kuddus, Md Abdul; Kulimbet, Mukhtar; Kumar, Nithin; Kumar Lal, Dharmesh; Landires, Iván; Latief, Kamaluddin; Le, Trang Diep Thanh; Le, Thao Thi Thu; Ledda , Caterina; Lee, Munjae; Lee, Seung Won; Lerango, Temesgen L.; Lim, Stephen S.; Liu, Chaojie; Liu, Xuefeng; Lopukhov, Platon D.; Luo, Hong; Lv, Hengliang; Mahajan, Preetam Bhalchandra; Mahboobipour, Ali; Majeed, Azeem; Malakan Rad, Elaheh; Malhotra, Kashish; Malik, Muhammad Sajeel Ahmed; Malinga, Lesibana Anthony; Mallhi, Tauqeer Hussain; Manilal, Aseer; Martinez-Guerra , Bernardo Alfonso; Martins-Melo, Francisco Rogerlândio; Marzo, Roy Rillera; Masoumi-Asl, Hossein; Mathur, Vasundhara; Maude, Richard James; Mehrotra, Ravi; Memish, Ziad A.; Mendoza, Walter; Menezes, Ritesh G.; Merza, Muayad Aghali; Mestrovic, Tomislav; Mhlanga, Laurette; Misra, Sanjeev; Misra, Arup Kumar; Mithra, Prasanna; Moazen, Babak; Mohammed, Hussen; Mokdad, Ali H.; Monasta, Lorenzo; Moore, Catrin E.; Mousavi, Parsa; Mulita, Francesk; Musaigwa, Fungai; Muthusamy, Raman; Naghavi, Ahamarshan Jayaraman; Naik, Pirouz; Naik, Ganesh R.; Naik, Gurudatta; Nair, Sanjeev; Nair, Tapas Sadasivan; Natto, Zuhair S.; Nayak, Biswa Prakash; Negash, Hadush; Nguyen, Dang H.; Nguyen, Van Thanh; Niazi, Robina Khan; Nnaji, Chukwudi A.; Nnyanzi, Lawrence Achilles; Noman, Efaq Ali; Nomura, Shuhei; Oancea, Bogdan; Obamiro, Kehinde O.; Odetokun, Ismail A.; Odo Odo, Daniel Bogale; Odukoya, Oluwakemi Ololade; Oh, In-Hwan; Okereke, Chukwuma O.; Okonji, Osaretin Christabel; Oren, Eyal; Ortiz-Brizuela, Edgar; Osuagwu, Uchechukwu Levi; Ouyahia, Amel; P A, Mahesh Padukudru; Parija, Pragyan Paramita; Parikh, Romil R.; Park, Seoyeon; Parthasarathi, Ashwaghosha; Patil, Shankargouda; Pawar, Shrikant; Peng, Minjin; Pepito, Veincent Christian Filipino; Peprah, Prince; Perdigão, João; Perico, Norberto; Pham, Hoang Tran; Postma, Maarten J.; Prabhu, Attur Ravindra Attur; Prasad, Manya; Prashant, Akila; Prates, Elton Junio Sady; Rahim, Fakher; Rahman, Mosiur; Rahman, Muhammad Aziz; Rahmati, Masoud; Rajaa, Sathish; Ramasamy, Shakthi Kumaran; Rao, Indu Ramachandra; Rao, Sowmya J.; Rapaka, Deepthi; Rashid, Ahmed Mustafa; Ratan, Zubair Ahmed; Ravikumar, Nakul; Rawaf, Salman; Reddy, Murali Mohan Rama Krishna; Redwan, Elrashdy Moustafa Mohamed; Remuzzi, Giuseppe; Reyes, Luis Felipe; Rezaei, Nazila; Rezaeian, Mohsen; Rezahosseini, Omid; Rodrigues, Mónica; Roy, Priyanka; Ruela , Guilherme de Andrade; Sabour, Siamak; Saddik, Basema; Saeed, Umar; Safi, Sher Zaman; Saheb Sharif-Askari , Narjes; Saheb Sharif-Askari , Fatemeh; Sahebkar, Amirhossein; Sahiledengle, Biniyam; Sahoo, Soumya Swaroop; Salam, Nasir; Salami, Afeez Abolarinwa; Saleem, Samreen; Saleh, Mohamed A.; Samadi Kafil, Hossein; Samadzadeh, Sara; Samodra, Yoseph Leonardo; Sanjeev, Rama Krishna; Saravanan, Aswini; Sawyer, Susan M.; Selvaraj, Siddharthan; Senapati, Sabyasachi; Senthilkumaran, Subramanian; Shah, Pritik A.; Shahid, Samiah; Shaikh, Masood Ali; Sham, Sunder; Shamshirgaran, Mohammad Ali; Shanawaz, Mohd; Sharath, Medha; Sherchan, Samendra P.; Shetty, Ranjitha S.; Shirzad-Aski, Hesamaddin; Shittu, Aminu; Siddig, Emmanuel Edwar; Silva, João Pedro; Singh, Surjit; Singh, Paramdeep; Singh, Harpreet; Singh, Jasvinder A.; Siraj, Md Shahjahan; Siswanto, Siswanto; Solanki, Ranjan; Solomon, Yonatan; Joan B.; Sreeramareddy, Chandrashekhar T.; Srivastava, Vijay Kumar; Steiropoulos, Paschalis; Swain, Chandan Kumar; Tabuchi, Takahiro; Tampa, Mircea; Jacques J.L. Lukenze, Tamuzi; Tat, Nathan Y.; Tavakoli Oliaee, Razieh; Teklay, Gebrehiwot; Tesfaye, Edosa Geta; Tessema, Belay; Thangaraju, Pugazhenthan; Thapar, Rekha; Thum, Chern Choong Chern; Ticoalu, Jansje Henny Vera; Tleyjeh, Imad M.; Tobe-Gai, Ruoyan; Toma, Temesgen Mohammed; Tram, Khai Hoan; Udoakang, Aniefiok John; Umar, , , , , , , , Tungki Pratama; Umeokonkwo, Chukwuma David; Vahabi, Seyed Mohammad; Vaithinathan, Asokan Govindaraj; Van Boven, Job F.M.; Varthya, Shoban Babu; Wang, Ziyue; Warsame, Muktar S.A.; Westerman, Ronny; Wonde, Tewodros Eshete; Yaghoubi, Sajad; Yi, Siyan; Yiğit, Vahit; Yon, Dong Keon; Yonemoto, Naohiro; Yu, Chuanhua; Zakham, Fathiah; Zangiabadian, Moein; Zeukeng, Francis; Zhang , Haijun; Zhao, Yang; Zheng, Peng; Zielińska, Magdalena; Salomon, Joshua A.; Reiner Jr, Robert C.; Naghavi, Mohsen; Vos, Theo; Hay, Simon I.; Murray, Christopher J.L.; Kyu, Hmwe Hmwe; Soriano, Joan B.; Atre; Aujayeb; Azadi; Azadnajafabad; Sina (Elsevier, 2024-07)
BACKGROUND : Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020. METHODS : We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990-2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data. FINDINGDS : We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5-14 years, 6·29% (5·05 to 7·70) in those aged 15-49 years, 5·72% (4·02 to 7·39) in those aged 50-69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5-14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15-49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50-69 years, and a 3·29% (-5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (-713 to 2180) fewer deaths. INTERPRETATION : Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups.

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